The purpose of this project is to study the mechanisms involving protein phosphorylation and dephosphorylation that regulate contractility and glycogenolysis in the intact mammalian heart. The primary emphasis is on understanding how these mechanisms are regulated in the myocardium and to relate the operation of these mechanisms to the physiological functions of cardiac tissue. One objective is to relate the formation of cyclic nucleotides, the activation of protein kinases and phosphorylase kinase and the phosphorylation of sarcoplasmic reticulum and sarcolemmal membranes, troponin and myosin light chains to the action of inotropic interventions such as norepinephrine, acetylcholine, anoxia, paired stimulation and alterations in the frequency of contraction on myocardial contractile function using isolated perfused hearts and papillary muscles. The importance of phosphorylation-dephosphorylation on the binding and uptake of calcium and the ATPase activities of these membranes and contractile proteins will be investigated. The mechanisms involved in the propagation of inotropic stimuli from one myocardial cell to another as well as cardiac desensitization will be studied. Using the same preparations subjected to these interventions another objective is to study the activation of glycogenolysis with the supposition that the mechanisms controlling mechanical performance and glycogenolysis have a common step of control through the effects of purine cyclic nucleotides on protein kinase and phosphorylase kinase but may be subsequently different. The role of calcium in the control of performance and glycogenolysis will also be investigated.